Downregulation of Proteinase-Activated Receptor-2, Interleukin-17, and Other Proinflammatory Genes by Subantimicrobial Doxycycline Dose in a Rat Periodontitis Model

Abstract

Background: Subantimicrobial dose doxycycline (SDD) has been used as an adjunct in periodontal treatment because of its matrix metalloproteinase inhibition properties. Although the benefits of SDD therapy, such as improvement in the parameters of periodontal probing depth and clinical attachment level, have been proven in multiple clinical studies, the comprehension of other biologic mechanisms of action on periodontitis remains poorly investigated. Therefore, this animal-model study evaluated the effects of SDD monotherapy on the expressions of the following key proinflammatory genes: proteinase-activated receptor-2 (PAR(2)), tumor necrosis factor (TNF)-alpha, interleukin (IL)-17, and IL-1 beta. Methods: Male Wistar rats were assigned randomly to the following: 1) control group: no ligature-induced periodontitis and no treatment; 2) ligature group: ligature-induced periodontitis and placebo treatment; and 3) ligature + doxycycline group: ligature-induced periodontitis and SDD treatment. After the experimental time, animals were sacrificed, and reverse transcription-polymerase chain reaction was performed to analyze the mRNA expression of IL-1 beta, IL-17, TNF-alpha, and PAR(2) in gingival tissue samples. Histologic analyses were performed on the furcation region and mesial gingiva of mandibular first molars to measure periodontal bone loss and collagen content. Results: SDD administration significantly downregulated PAR(2), IL-17, TNF-alpha, and IL-1 beta mRNA expressions (P < 0.05). In addition, SDD treatment was accompanied by lower rates of alveolar bone loss (P < 0.05) and maintenance of the amount of gingival collagen fibers. Conclusion: These findings reveal new perspectives regarding SDD efficacy because it can be partially related to proinflammatory gene expression modulation, even considering PAR(2) and IL-17, which has not been investigated thus far.